| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology |
The Second Department of Surgery, Shimane Medical University, Izumo 693-8501, Japan
Heparan sulfate plays an essential role for insolubility of the components of extracellular matrix and represents a storage depot for various growth factors. Therefore, heparanase produced by a given tumor may facilitate tumor invasiveness and angiogenesis through the release of heparan sulfate-bound growth factors. Although the growth factors responsible for angiogenesis in hepatocellular carcinoma (HCC) have recently been investigated, the clinicopathological significance of heparanase in connection with basic fibroblast growth factor (bFGF) expression in HCC has not been evaluated so far.
Fifty-five patients who had undergone hepatic resection for HCC without preoperative treatment were included in the present study. Expression of heparanase mRNA was evaluated by reverse transcription-PCR, and bFGF was examined by Western blotting using a monoclonal antibody. Tumor angiogenesis was evaluated by immunostaining with a factor VIII-related monoclonal antibody. Expression of heparanase mRNA was detected in 47% of HCCs and was significantly correlated with larger tumor size (P = 0.01), presence of portal vein invasion (P = 0.01), and higher overall tumor invasiveness (P = 0.02). Moreover, its expression was correlated with tumor microvessel density (MVD; P = 0.02). There was a direct correlation between the levels of bFGF proteins and MVD in HCCs (P = 0.0001), and, furthermore, concomitant expression of bFGF and heparanase was associated with higher tumor MVD as compared with expression of either factor alone (P = 0.01).
In conclusion, the expression of heparanase in HCC enhances growth, invasion, and angiogenesis of the tumor, and bFGF seems to be a potent angiogenic factor for HCC.
This article has been cited by other articles:
|
|
 |
|
  R. W. C. Pang, J. W. Joh, P. J. Johnson, M. Monden, T. M. Pawlik, and R. T. P. Poon Biology of Hepatocellular Carcinoma Ann. Surg. Oncol., April 1, 2008; 15(4): 962 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Simizu, T. Suzuki, M. Muroi, N. S. Lai, S. Takagi, N. Dohmae, and H. Osada Involvement of Disulfide Bond Formation in the Activation of Heparanase Cancer Res., August 15, 2007; 67(16): 7841 - 7849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zetser, Y. Bashenko, E. Edovitsky, F. Levy-Adam, I. Vlodavsky, and N. Ilan Heparanase Induces Vascular Endothelial Growth Factor Expression: Correlation with p38 Phosphorylation Levels and Src Activation Cancer Res., February 1, 2006; 66(3): 1455 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Okawa, Y. Naomoto, T. Nobuhisa, M. Takaoka, T. Motoki, Y. Shirakawa, T. Yamatsuji, H. Inoue, M. Ouchida, M. Gunduz, et al. Heparanase Is Involved in Angiogenesis in Esophageal Cancer through Induction of Cyclooxygenase-2 Clin. Cancer Res., November 15, 2005; 11(22): 7995 - 8005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Naggi, B. Casu, M. Perez, G. Torri, G. Cassinelli, S. Penco, C. Pisano, G. Giannini, R. Ishai-Michaeli, and I. Vlodavsky Modulation of the Heparanase-inhibiting Activity of Heparin through Selective Desulfation, Graded N-Acetylation, and Glycol Splitting J. Biol. Chem., April 1, 2005; 280(13): 12103 - 12113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zcharia, R. Zilka, A. Yaar, O. Yacoby-Zeevi, A. Zetser, S. Metzger, R. Sarid, A. Naggi, B. Casu, N. Ilan, et al. Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models FASEB J, February 1, 2005; 19(2): 211 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gingis-Velitski, A. Zetser, V. Kaplan, O. Ben-Zaken, E. Cohen, F. Levy-Adam, Y. Bashenko, M. Y. Flugelman, I. Vlodavsky, and N. Ilan Heparanase Uptake Is Mediated by Cell Membrane Heparan Sulfate Proteoglycans J. Biol. Chem., October 15, 2004; 279(42): 44084 - 44092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gingis-Velitski, A. Zetser, M. Y. Flugelman, I. Vlodavsky, and N. Ilan Heparanase Induces Endothelial Cell Migration via Protein Kinase B/Akt Activation J. Biol. Chem., May 28, 2004; 279(22): 23536 - 23541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zetser, F. Levy-Adam, V. Kaplan, S. Gingis-Velitski, Y. Bashenko, S. Schubert, M. Y. Flugelman, I. Vlodavsky, and N. Ilan Processing and activation of latent heparanase occurs in lysosomes J. Cell Sci., May 1, 2004; 117(11): 2249 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Simizu, K. Ishida, M. K. Wierzba, and H. Osada Secretion of Heparanase Protein Is Regulated by Glycosylation in Human Tumor Cell Lines J. Biol. Chem., January 23, 2004; 279(4): 2697 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kelly, H.-Q. Miao, Y. Yang, E. Navarro, P. Kussie, Y. Huang, V. MacLeod, J. Casciano, L. Joseph, F. Zhan, et al. High Heparanase Activity in Multiple Myeloma Is Associated with Elevated Microvessel Density Cancer Res., December 15, 2003; 63(24): 8749 - 8756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, R. M. Quiros, J. B. Maxhimer, P. Jiang, R. Marcinek, K. B. Ain, J. L. Platt, J. Shen, P. Gattuso, and R. A. Prinz Inverse Correlation between Heparan Sulfate Composition and Heparanase-1 Gene Expression in Thyroid Papillary Carcinomas: A Potential Role in Tumor Metastasis Clin. Cancer Res., December 1, 2003; 9(16): 5968 - 5979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zetser, Y. Bashenko, H.-Q. Miao, I. Vlodavsky, and N. Ilan Heparanase Affects Adhesive and Tumorigenic Potential of Human Glioma Cells Cancer Res., November 15, 2003; 63(22): 7733 - 7741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shinyo, J. Kodama, A. Hongo, M. Yoshinouchi, and Y. Hiramatsu Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer Ann. Onc., October 1, 2003; 14(10): 1505 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ikeguchi, K. Fukuda, K.-i. Yamaguchi, A. Kondo, S.-i. Tsujitani, and N. Kaibara Quantitative Analysis of Heparanase Gene Expression in Esophageal Squamous Cell Carcinoma Ann. Surg. Oncol., April 1, 2003; 10(3): 297 - 304. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
